Glucose-6-phosphate-dehydrogenase on old peroxisomes maintains self-renewal of epithelial stem cells after asymmetric cell division

Hien Bui, Simon Andersson, Agustin Sola-Carvajal, Tommaso Marchi, Eliisa Vähäkangas, Minna Holopainen, Andrew H. House, Bohdana M. Rovenko, Johanna I. Englund, Maria Kasper, Emilia Kuuluvainen, Reijo Käkelä, Ville Hietakangas, Emma Niméus and Pekka Katajisto ()
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Hien Bui: University of Helsinki
Simon Andersson: University of Helsinki
Agustin Sola-Carvajal: Karolinska Institutet
Tommaso Marchi: Lund University
Eliisa Vähäkangas: University of Helsinki
Minna Holopainen: University of Helsinki
Andrew H. House: University of Helsinki
Bohdana M. Rovenko: University of Helsinki
Johanna I. Englund: University of Helsinki
Maria Kasper: Karolinska Institutet
Emilia Kuuluvainen: University of Helsinki
Reijo Käkelä: University of Helsinki
Ville Hietakangas: University of Helsinki
Emma Niméus: Lund University
Pekka Katajisto: University of Helsinki

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Selective inheritance of sub-cellular components has emerged as a mechanism guiding stem cell fate after asymmetric cell divisions. Peroxisomes play a crucial role in multiple metabolic processes such as fatty acid metabolism and reactive oxygen species detoxification, but the apportioning of peroxisomes during stem cell division remains understudied. Here, we develop a mouse model and labeling technique to follow the dynamics of distinct peroxisome age-classes, and find that old peroxisomes are inherited by the daughter cell retaining full stem cell potency in mammary and epidermal stem cell divisions. Old peroxisomes carry Glucose-6-phosphate-dehydrogenase, whose specific location on the peroxisomal membrane promotes stem cell function by facilitating peroxisomal ether lipid synthesis. Our study demonstrates age-selective apportioning of peroxisomes in vivo, and unveils how functional heterogeneity of peroxisomes is utilized by asymmetrically dividing cells to metabolically divert the fate of the two daughter cells.

Date: 2025
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DOI: 10.1038/s41467-025-58752-z

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